Helicobacter pylori modulates lymphoepithelial cell interactions leading to epithelial cell damage through Fas/Fas ligand interactions

Helicobacter pylori causes a common chronic infection of humans that leads to epithelial cell damage. Studies have shown that apoptosis of the gastric epithelium is increased during infection and this response is associated w ith an expansion of gastric T-helper type 1 (Th1) cells. We report that gas tric T cells contribute to apoptosis of the epithelium by a Fas/Fas ligand (FasL) interaction. Pas receptor expression was detected on freshly isolate d gastric epithelial tells by dow cytometry and immunohistochemistry, and t his level of expression was increased during infection with H, pylori. The expression of Pas receptor on three gastric epithelial cell lines was incre ased by N, pylori, either alone or in combination with gamma interferon or tumor necrosis factor alpha. The role of Fas in apoptosis of gastric epithe lial cell lines was evidenced by DNA fragmentation after crosslinking of Pa s with specific antibodies. Fast expression was detected by immunohistochem istry on mononuclear cells in gastric biopsy specimens of infected but not uninfected subjects. Gastric T-cell lines were also shown to express Fast, as evidenced by reverse transcription-PCR and killing of target cells expre ssing Pas receptor. Moreover, these T-cell lines were capable of killing cu ltured gastric epithelial target cells and antibodies that block the intera ction between Pas receptor and Fast inhibited this cytotoxic activity. Thes e observations demonstrate that local Th1 cells may contribute to the patho genesis of gastric disease during H. pylori infection by increasing the exp ression of Pas on gastric epithelial cells and inducing apoptosis through F as/FasL interactions.